Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 710

11.5.5.5 Integrins

Migrating cells adhere to the crossed matrix. The role of integrins vary according to
the traversed medium and chemoattractant type. Neutrophil chemotaxis depends on
β 2 -integrins. In response to TNF

α , neutrophil extravasation relies on α L β 2 -integrin,

whereas α M β 2 -integrin slows down neutrophil extravasation [ 1444 ]. On the other

hand, α M β 2 -integrin is the predominant integrin involved in chemotaxis through

synovial and dermal fibroblast barriers [ 1444 ].
Integrin-

α 4 is expressed at low levels on human neutrophils. It may repress
neutrophil chemotaxis [ 1444 ]. It impedes B cells from leaving the spleen marginal
zone. On the other hand, it enables the recruitment of T cells and eosinophils in
inflammation sites. Integrins regulate chemotaxis owing to their dual roles as both
cell adhesion molecules and signal transducers.

11.5.6 Inflammatory Mediators

Inflammation involves mediators released by damaged tissue, generated by plasma
enzymes, and produced by leukocytes. Activated Toll-like receptors, cytokines, as
well as inflammation messengers such as angiotensin-2 activate nuclear factor- κ B

factor. Transcription factor NF B acts as an integrator that controls initial steps of

inflammation — leukocyte extravasation and chemotaxis — using canonical and
non-canonical pathways, as well as monocyte activation owing to interleukin-6 and
signal transducer and activator of transcription STAT3 [ 1446 ].

κ

11.5.6.1 Toll-like Receptors

Inflammation is a process during which immunocytes are recruited to sites of infec-
tion and injury. Sensors of infectious agents and transducers of inflammation include
pattern-recognition receptors such as Toll-like receptors that bind to pathogen-
associated molecules.
Toll-like receptors on antigen-presenting cells, especially macrophages and
dendritic cells, stimulated by pathogen-associated molecules, such as lipopolysac-
charide (LPS; ligand for TLR4) 34 and nucleic acids (ligands for TLR3, TLR7, TLR8
and TLR9), rapidly activate transcription factors, such as interferon-regulatory

34 Lipopolysaccharides of bacterial walls activate CD14-TLR4 complexes on the surface of
lymphocytes, macrophages, and dendritic cells. They then cause the secretion of inflamma-
tory cytokines, chemokines, and enzymes that mobilize immune effector cells and prime the
adaptive immune system. Multiple post-transcriptional regulations attenuate the production of
pro-inflammatory proteins to avoid excessive response by restricting mRNA stability and/or
translation [ 1456 ].